Localized delivery of therapeutic agents (e.g., intrathecally, intraspinally, intraarticularly, etc.) has become increasingly more popular over the years because it has several advantages over more conventional routes of drug delivery such as oral delivery. Localized delivery has the advantage of allowing the therapeutic agent to be implanted directly at the site where drug action is needed. This becomes especially important for drugs that have unwanted systemic side effects.
Localized delivery of therapeutic agents protects the therapeutic agent from first-pass metabolism (e.g., break down due to gastric and liver enzymes) and thus improves the drug's availability in vivo at the desired target site. This particular feature makes this technology particularly attractive for the delivery of labile drugs such as proteins and peptides. Extended release formulations that can be locally delivered can also improve patient compliance. For example, therapeutic agents can be encapsulated and delivered locally allowing the drug to be released over extended periods (e.g., 6 months or longer), thereby eliminating the need for multiple injections.
In the past, localized repeat delivery of therapeutic agents has been used to treat chronic debilitating diseases such as osteoarthritis. Osteoarthritis is a chronic condition that affects millions of people in the world and is a type of arthritis that is caused by the chronic breakdown and eventual loss of cartilage in one or more joints. Osteoarthritis often affects synovial joints, such as the knees, hips, fingers, thumbs, neck, and spine. Severe forms of the disease are extremely disabling and restrict a patient's lifestyle. Localized delivery via intraarticular injection of corticosteroids, hyaluronan or hylan provide some short term relief in controlling the pain symptoms of osteoarthritis.
Sciatica, another chronic debilitating disease, can be a painful condition associated with the sciatic nerve which runs from the lower part of the spinal cord (the lumbar region), down the back of the leg and to the foot. Sciatica generally begins with a herniated disc, which later leads to local immune system activation. The herniated disc also may damage the nerve root by pinching or compressing it, leading to additional immune system activation in the area. In the past, localized delivery of corticosteroids (e.g., epidural) has been used to provide short term relief of the inflammation and pain associated with sciatica.
Newer methods are currently being investigated for treatment of chronic debilitating diseases utilizing localized delivery of drug depots. In these treatments typically the drug depot is delivered locally to the treatment site and the drug is released from the depot in a relatively uniform dose over weeks, months or even years. Localized delivery of drug depots is becoming especially important and popular in modulating the immune, inflammation and/or pain responses in treatment of chronic diseases.
Sometimes after the drug depot is implanted at the treatment site, unfortunately, the drug depot may migrate from the implant site prior to surgical closure (e.g. floats off in the blood or shifts as tissues are repositioned during surgical site closure) or as physiological conditions change (e.g., repair and regeneration of cells, tissue in growth, movement at the implant site, etc.). At times, this may reduce the efficacy of the drug as the drug depot migrates away from the implant site and lodges in a distant site. If this occurs, often the drug depot will have to be removed from the distant site and be reinserted causing additional physical and psychological trauma to a patient. In some cases, if the drug depot migrates into a joint, the drug depot may inhibit movement. In more severe cases, if the drug depot migrates into a blood vessel, it may restrict blood flow causing an ischemic event (e.g., embolism, necrosis, infarction, etc.), which could be detrimental to the patient.
In other cases there is no drug depot formulation on the market, for example epidural delivery of corticosteroids. In this case the drug is typically injected near the site of inflammation, but rapidly diffuse away from the injection site. Likewise, injection of the drug near the site of inflammation is important in achieving the best clinical outcome, but it is difficult to determine the precise location of the needle tip during injection and therefore the precise placement of the drug.
New drug depot compositions and methods are needed, which can easily allow for the accurate and precise placement of a drug with minimal physical and psychological trauma to a patient and that retain the drug at the desired target location longer. In addition, drug compositions and methods are needed that accurately and precisely allow placement of the drug depot in a manner that optimizes location, accurate spacing, and drug distribution.